title: HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency.
abstract: BACKGROUND
  Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent investigations suggest that HLA-B*5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B*5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population. Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity.
  
  
  METHODS
  We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010.
  
  
  RESULTS
  Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 [18% in HLA-B58 (+) versus 0% in HLA-B58 (-)]. Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol.
  
  
  CONCLUSIONS
  In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Jung
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Song
authors.forename: Yon-Su
authors.initials: YS
authors.lastname: Kim
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.forename: Sae-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
mesh_terms: D000293:Adolescent; D000328:Adult; D000493:Allopurinol / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism*; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D056910:Republic of Korea; D012189:Retrospective Studies; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D015235:HLA-B Antigens; C562005:HLA-B58; D000493:Allopurinol